Fiebre mediterránea familiar sin fiebre recurrente / No disponible

Describimos el caso de una paciente con historia de pericarditis recurrentes de 16 años de evolución sin fiebre objetivable ni de patrón recurrente. Se le realizan múltiples estudios tratando de averiguar la etiología de la enfermedad. Finalmente, surge la sospecha de fiebre mediterránea familiar con la confirmación diagnostica de la amplificación genética específica de los exones 2 y 10 del gen MEFV. Destacamos la importancia de la sospecha diagnóstica en casos atípicos (AU)

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Intrauterine device may trigger typical attacks of familial Mediterranean fever: a case report.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by episodic, recurrent, self-limited attacks of fever and serositis (sterile peritonitis, pleuritis, arthritis, etc). The insufficiency in restriction of mild inflammation contributes this consequence in FMF.Intrauterine devices (IUDs) have been widely used in the world for contraception by gynecologists as an effective and safe method. Herein, we present a woman with FMF as the first case, whose attacks were triggered by copper-containing IUD. Our hypothesis in the present case was that sterile mild inflammation in the uterus caused by copper-containing IUD may be the initial source of systemic inflammatory response.In our opinion, clinicians should consider that the copper-containing IUDs may be another cause of FMF attacks in women using this contraceptive method.

[Auto-inflammatory syndromes and pregnancy]. / Syndromes auto-inflammatoires et grossesse.

In familial mediterranean fever (FMF), fertility is normal in treated patients. There is no abnormality of spermatogenesis under usual therapeutic doses of colchicine. The risk of early abortion is increased if inflammatory attacks occur during the pregnancy. It is recommended to continue colchicine treatment during the conception and the pregnancy. Careful follow-up must be organized, even more in patients with renal amyloidosis. Breast-feeding is allowed under colchicine with no risk for the baby. There is no indication for systematic amniocentesis in FMF patients treated with colchicine.

The pharmacologic basis of treatment with colchicine in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the prototype of auto-inflammatory disorders and is ethnically restricted to people living in the Mediterranean basin and Middle-East. Pyrin, the protein product of the FMF gene, expressed in myeloid cells and fibroblasts, interacts with the cytoskeletal machinery and may modulate leukocyte effector functions. At present colchicine, an alkaloid with antimitotic activity interfering with microtubule formation, which has been used to alleviate acute gout, is the only available drug for patients with FMF to prevent both acute attacks and long-term complications such as amyloidosis. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules, but also through changes at the transcriptional level influencing cell cycle regulation and leukocyte migration. Gastrointestinal side effects may occur early and are the most frequent manifestations of colchicine toxicity in children, whilst multiple organ failure is very rarely reported as overdosage expression.

Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update.

Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg/die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

Late diagnosis of severe colchicine intoxication.

A 4-year-old Turkish girl was referred to our hospital with the findings of encephalopathy and pancytopenia. She had a history of severe abdominal cramps and gastrointestinal bleeding. A confused state, muscle pain and weakness, erythema-bullous and erythema-nodosum-like skin lesions, and alopecia were observed at her hospitalization. All of these symptoms resolved on follow-up. On laboratory investigation severe thrombocytopenia and leukopenia, mild anemia, a moderate increase in aspartate aminotransferase and alanine aminotransferase levels were detected. After reevaluating her medical history, it was learned that she had accidentally taken 1.3 to 1.5 mg/kg of colchicine 3 to 4 days before her first hospitalization. The possibility of misdiagnosis of colchicine intoxication should be borne in mind, and pediatricians must be aware of its toxic effects, especially in areas where patients with familial Mediterranean fever are present.

Prevalence of ischemic heart disease in patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever is a genetic disorder manifested by recurrent attacks of peritonitis, pleuritis and arthritis, and characterized by clinical, histological and laboratory evidence for localized and systemic inflammation. Colchicine treatment usually prevents the attacks and the associated inflammation. Inflammation may play an important role in the initiation and progression of atherosclerosis and ischemic heart disease. OBJECTIVE: To study the effect of inflammation and its prevention on the occurrence of IHD, using FMF as a model. METHODS AND PATIENTS: We studied the presence of IHD and its risk factors in 290 FMF patients aged 40 years or more, and in two control groups--233 spouses of the FMF patients, and 126 patients with inflammatory diseases obtained from other outpatient clinics, FMF patients were also compared with age and gender-matched individuals from the population reference data of the Israel Ministry of Health. RESULTS: The prevalence of IHD in FMF patients was significantly lower than in the group of controls from other outpatient clinics (15.5% vs. 30.2%, P < 0.05) and comparable with their spouses (11.2%) and with the matched general population in Israel (16%). CONCLUSIONS: These findings suggest that despite the evidence of recurrent inflammation, colchicine-treated FMF patients are not more predisposed to IHD than the normal population.

Long-term colchicine treatment in children with familial Mediterranean fever.

Three hundred fifty children (younger than age 16) who had familial Mediterranean fever (FMF) were given continuous prophylactic treatment with colchicine (1-2 mg/day) for 6-13 years. Complete remission of febrile attacks was achieved in 64% of the patients, and partial remission in 31%. Protracted attacks of arthritis virtually disappeared. None of the children developed amyloidosis while on the colchicine regimen. Side effects of colchicine were insignificant, and did not prompt permanent discontinuation of treatment in any of the children. Their growth, development, and subsequent fertility were normal. The efficacy of long-term colchicine treatment of children with FMF makes early diagnosis life saving.

Metaraminol provocative test: a specific diagnostic test for familial Mediterranean fever.

The diagnosis of familial Mediterranean fever has been one of exclusion. In a placebo-controlled, double-blind, cross-over study a challenge with a 10 mg dose of metaraminol infusion was followed within 48 h by a typical disease-like attack in all of 21 patients with familial Mediterranean fever but in none of 21 control subjects. The induced attacks were milder and of shorter duration than the spontaneous ones. The metaraminol-induced symptoms were similar to the natural disease attacks and could be prevented with prophylactic colchicine therapy. No significant side-effects were observed.

Colchicine use for familial Mediterranean fever. Observations associated with long-term treatment.

Of 85 patients with familial Mediterranean fever receiving continuous prophylactic colchicine therapy, 62 (73 percent) have had a significant reduction in the severity and frequency of their attacks. All 62 have been observed for three years or more, for a total of 4,680 patient-months and a mean duration of 75.5 months. Of the 85 patients, 23 (27 percent) did not complete three years of treatment for a variety of reasons. Diarrhea was the most common side effect, necessitating reduction of colchicine dosage in 12 patients, but discontinuation of treatment in only one. No other significant side effects were observed. Continuous, prophylactic colchicine therapy is effective in preventing the recurrent febrile paroxysms of familial Mediterranean fever and is indicated in those patients who are incapacitated by frequent attacks or who are at risk for amyloidosis developing.

Long-term colchicine therapy of familial Mediterranean fever.

Familial Mediterranean fever is a disorder characterized by recurrent fever and polyserositis. Continuous prophylactic colchicine therapy has been effective in suppressing attacks in affected adults. From 30 children with FMF, 14 were selected for colchicine therapy. Eight children continued prophylactic colchicine therapy for 29 months (mean) and experienced a marked decrease in the frequency of attacks. Six other children did not comply with the treatment regimen. Although no deleterious side effects were noted, the safety of long-term colchicine administration in childhood is unknown.

Effect of prophylactic colchicine therapy on leukocyte function in patients with familial Mediterranean fever.

Patients with familial Mediterranean fever (FMF) who were part of a double-blind trial of daily colchicine as prophylaxis for their disease had leukocyte functions studied while receiving colchicine or placebo. Leukocytes taken from these patients while on prophylactic doses of colchicine produced normal quantities of leukocytic pyrogen, ingested bacteria normally, and migrated normally in chemotatic chambers. In addition these patients had normal numbers of circulating T and B lymphocytes as well as normal blastogenic reponses of their peripheral lymphocytes to mitogenic stimuli. The patients on colchicine, however, had significantly fewer neutrophils and monocytes accumulating at skin-window sites 24 hours after the initial abrasion. Because the early phase of the skin-window response was normal in these patients, the decreased late response may be related to a failure to amplify the initial inflammatory reaction. The reduced capacity to generate a normal inflammatory response may account for the failure of these patients to develop full attacks while taking colchicine.